Purpose Bones have a complex hierarchical structure that supports their diverse chemical, biological, and mechanical functions. High rates of bone susceptibility to fractures and injury have attracted extensive research interest to find alternate biomaterials for bone scaffolds. Natural bone healing is only successful if the defect is very small and when a defect exceeds 1 cm 3 then bone grafting is required. Large bone defects or injuries are very serious problems in orthopedics as they bring great harm to health and normal function of daily life routine. A scaffold should have good strength to maintain its own structure after implantation in a load bearing environment and without being stiff that shields surrounding bone from the load. Therefore, mechanical properties of bone scaffolds should match those of the host tissue and should be part of the natural environment of the body without any harm or further damage. Methods In this paper, we present two main contributions. First, we investigate the use of machine learning models in identifying biomaterials that are suitable for bone scaffolds. Second, we rank the best materials for biomedical scaffold applications using the multi-criteria decision analysis methods, the Preference Ranking Organization METhod for the Enrichment of Evaluations (PROMETHEE). Machine learning models investigated are AdaBoost, artificial neural network (ANN), Naïve Bayes (NB), Decision tree (DT), Support Vector Machine (SVM), and K-Nearest Neighbor (KNN). Mechanical properties such as comprehensive strength, tensile strength, and Young’s modulus with the cortical bone are used as the standard reference for classification. Results The results show that the ANN outperforms the other machine learning models in identifying the biomaterials suitable for bone tissue engineering, while the ranking results using PROMETHEE show that Brushite and Titanium alloy are the best appropriate biomaterials for the cancellous and cortical bones, respectively. Conclusion Brushite and Titanium alloy are the best biomaterials for the cancellous and cortical bones, respectively.